Going Dutch

Saturday, May 22, 2010

My cousin posted a request on my facebook wall for my thoughts on the synthetic cell news. I'm answering by blog because I'm still shocked and appalled with the recent revelations that Mark Zuckerberg is going to sell the name of the high school I attended to the Kraft marketing department for something like 40 million dollars.

I'm considering the issues and controversy surrounding this new strain of mycoplasma, the smallest known organism, now being entirely driven by a synthetically created genome in a lab run by Craig Venter. Additionally, since I think that one reason why the general public maintains this area as such a hotbed of brawl is that many scientists like to awe their audiences by explaining things in terms that no one can understand, leaving the ordinary lay person with just their imaginations. I don't think this is the right approach, and I hope to be able to describe the science in a coherent manner. But in terms of the issues surrounding the synthetic cell, I think they can be broken down to potential benefits (including both human health and agriculture/energy), potential hazards (terrorism and epidemics), and the moral question of playing God.

What Venter's group did was to piece together a mycoplasma genome designed using only a skeleton crew of genes required for the organism to live, remove the genome of a natural mycoplasma, and inject the new synthetically created genome. The first thing to point out is that this kind of genetic manipulation has been going on for a long time, where in essence scientists harness the machinery of a living cell to respond to and interact with whatever gene or genes you care to transmit into it. Artificial DNA has been shuttled into all different sorts of cells, plants, and animals for years. Moreover, entire genomes have been replaced by others by our hand (we've cloned mice, sheep, even humans if only the Raelians hadn't been called back to the mothership). What's unique about this event is that the entire genome being replaced in the mycoplasma is artificial. But to say that we've made some huge leap in biological technology with this synthetic cell is inaccurate.

But what is huge is the future potential.

Venter has a vision where he repeats the same procedure on algae, using a stitched-together genome whereby the new synthetic cell would consume CO2 and emit biofuel. Exxon has promised his company something like $600 million if he succeeds. The other major use in the health care industry is practically limitless in scope. Insulin-producing cells for diabetics, healthy blood stem cells for leukemia patients, degenerative diseases cured, spinal cord injuries gone...all possible. Abundant and sustainably designed crops, nanotechnology, everything Gibson and Stephenson wrote about, all likely.

Sounds great, right? As a biological scientist I can say with absolute certainty that yes, the possibilities flood my mind. Especially given the current work I'm doing unraveling a signaling pathway that keeps cells in an undifferentiated stem cell-like state, it's tremendously exciting to think about the potentials. And yet like everything, the fact that there are so many possibilities means that the potential for harm may likely come from a direction we never considered.

The scary flipside to the fact that this technology is not wildly difficult to carry out, coupled to the public availability of every gene sequence, is that it opens an avenue for harm which is as limitless as the potential benefits. And unfortunately, unlike nuclear non-proliferation treaties where the technology in question is rather complicated, the ability of a global genetically modified organism treaty to effectively suppress bioterrorism is pretty low. The technology to create a genome expressing whatever disease-causing gene you like is here, and the hundreds of sequences of these genes are all available to anyone with internet access. From this vantage point, the genie is already out of the bottle. What then would be able to stop some whackjob from creating an artificial viral genome in his basement that expresses an airborne HIV? Probably not much.

Equally as unsettling is the impact of unforeseen changes that may occur in the new genome. Venter's group took care to remove any known pathogenic elements from the mycoplasma genome they built, necessary steps to save the goats (a known animal to be infected by mycoplasma). Funny that didn't calm the bleating goat activists down, but their point isn't a baseless one. It's unknown what the effects could be if some spontaneous mutation changes the organism so that it goes viral resulting in something that infects the planet like kudzu and turns us into rapid zombies. Put that way sounds unlikely, however the fact remains that although we are able to translate the genetic code, the meaning behind it still remains mostly elusive. We know of many mutations that are linked to disease, but the mechanisms behind the mutations are still largely unknown. Thus it may absolutely be said that we scientists by tinkering with genomes are opening an untold number of Pandora's Boxes.

Well, yes, that is in fact our job. Most of the best discoveries in the lab have been because some researcher with a mischievous glint in their eye decided late one night to mix some things together just to see what happens. It's a rare event that a discovery of something anticipated occurs. So the day I stop tinkering is the day I'm out of a job.

The last issue about "playing God" I find to be something of an irritating knee-jerk reaction that may be due in part to the lack of education the public receives about genetic technology, which is unquestionably the industry's fault. First off, to reiterate, genetic manipulations have been occurring for years and so far as I know there are still no C.H.U.D.s after us. More importantly, I truly believe that our ability to grasp the technology and interpret the genetic code is in fact evolution, therefore it's in the natural order of things to be able to manipulate it as well. Clearly some government oversight is necessary such as for human cloning, but even more important is that counter-terrorism labs are established that stay one step ahead of technology that could cause potential harm. Ignoring the technology would be the worst course of action.

Overall though I think it's a great thing, I prefer Madam de Stael's suffering to boredom and think that facing these things head on is superior to head in sand. A careful and thoughtful approach is necessary, starting with how this technology is introduced to the public. I was struck the other day when I read the chirpy term "green biotechnology" to refer to the once ominous "genetically engineered crops". Discourse matters, and having a fearful, uninformed general populace helps no one. That's what we could focus on today, and hopefully by tomorrow, I will have figured out how to make these new mycoplasmas do my laundry.

Lastly, there's a great TED talk by Venter a couple of years ago where he discusses his project. You can find it here:http://www.ted.com/talks/craig_venter_unveils_synthetic_life.html

Sunday, May 9, 2010

My sister came to tour through Europe. For those of you who I haven't mentioned this to so many times you want to stuff cotton in your ears my sister is Amanda Palmer and she has a job as a rock star. Being the sister of someone whose job it is to be widely adored is a uniquely advantageous position, one that finds most of the lovely trappings without having to do any of the actual work. A fine example of this fact is the past week.

Amanda arrives in Amsterdam for a show in the middle of the European tour exhausted. The ashcloud had grounded her flight in, sadly, Iceland, and then forced upon her several ferries over the North Channel involving many sick bags. She has professed her disgust for the whole event by showing up in a tshirt loudly stating "F*CK THE ASHCLOUD". She is not very shy, my little sister. For her troubles she did, however, command an impressive headline in the Boston Globe which read something like, "Amanda Palmer Late, Still has Twitter Access". I'm still shaking my head.

Holly Gaiman has also arrived from London to work the merch table. Holly is the daughter of Amanda's fiancee, Neil Gaiman, a very nice man who writes for a living. I have felt very protective towards his daughter ever since I went to rescue her from a date in a London club my sister had auctioned her off on for $750.

The show in Amsterdam is a Wednesday night at the Melkweg, a club found on one of the city's many incredibly narrow streets across from a police station. The driver of the band's van celebrates this setting by smashing into the side of a police car parked on the street and breaking off the mirror. Apparently this happens all the time, and they are all released in time for sound check. The show begins with more of a musical theater act consisting of conjoined twins named Evelyn and Evelyn, the other twin being played by Amanda's sidekick for the tour, Jason Webley. They play a number of instruments with one of each of their hands including the piano, guitar, drums, accordion, and the ever-present ukulele. Even I, with less musical talent than Vanilla Ice, know that this must have taken an enormous amount of practice. A few more wrong notes than usual, but highly impressive nonetheless.

A lovely shadow puppet story explains the background of the twins and involves a murderous physician and a truckload of chickens. It is unfortunately marred by the stage getting the wrong light, which ends up incinerating the eyes of the entire left side of the floor audience. Then Jason and Amanda each play solo acts and that's it. The show has delighted the large number of students from my lab who I have saturated the guest list with, although I pay for it dearly the next day at work by everyone singing the "Chicken Man" song incessantly.

Speaking of the next day, my sister had asked if I would like to get on the van with them and drive to their next show in Hamburg and then onto Berlin for the weekend, where I already had a train ticket booked. I said no, I had to work, be a respectable citizen, excuses that led her to spit out that I needed much more rock and roll in my life. Perhaps she had a point, for I find myself sitting at my desk that day staring at the 98th draft of the paper that I still haven't submitted feeling like the biggest twit. Luckily Europe is famous for low budget airlines that you have never heard of, and within a few minutes I'm happily booked to Amanda's show in Prague the following week on the unfortunately named Wizz Air.

But first Berlin. It's Queensday in Holland as I take leave, much to my delight since this holiday turns the country into the equivalent of Bourbon Street on Mardi Gras except even worse because it's raining and everyone is wearing orange. Five hours of pleasant slack jawed window staring later I'm at the Berlin train station. This is another of the brilliant things about Europe, the trains. It's so quick and easy to step on and find yourself in the center of another country before you've even finished your beer in the club car. Of course it helps that I live in a tiny place bordered by three different countries, all of which I can see from my roof, but still. Love a good train ride.

Berlin is a very cool city. It has all of the magnificent grand old buildings that are found in most major European cities, but is also permeated with a more recent and fascinating history that can make the antiquity seem somewhat irrelevant.Our British cousin lives there with his wonderful German wife and kid, who were the gracious hosts of Amanda's birthday party that night. At least a dozen close friends and family members turn up including a guy playing a show that night whose band was subtly named Kill Hannah after his ex-girlfriend.

Amanda celebrates her birthday with true gusto and aplomb, the result of which is the necessity of a large blue bucket being present next to her on the stage the following night. Luckily she doesn't need to use it, but it's close. Watching her cringe and suffer this category five hangover under blistering spotlights and I have never been so glad not to be a rock star. Calling in sick one day just isn't an option. A car in Belfast once ran over and broke several bones in her foot yet she still hobbled on stage that night to do her job, whereas any other sensible person would have been propped up on ten pillows demanding ice cream and another Percocet.

It is therefore no surprise that when we meet up in Prague the next week she announces to me that she's quitting her job (this is something she assures me that she says at the end of every tour). However this time I believe her sentiments are exacerbated by the venue's poster of her, which looks like something you might receive at the deli counter if you ordered melons with Serrano ham. (If you look closely you can see her reflection seething). So I take her out for a nice Czech beer and she calms down.

Prague is a very beautiful city that like many other Eastern European cities maintains an eerie juxtaposition of lavish old empires frozen in time by the Iron Curtain. Like every American in her 20's I backpacked through Prague years ago, and was happy to find that the relative inexpensiveness of the city still held true. However so did the taxi scams, one of which attempted to charge me the equivalent of over €60 for a 3km fare. Only by threatening to call out my hotel concierge (in my experience, the only ones actually concerned about you getting ripped off and having a bad stay) did the driver let me out of the cab for a quarter the fare and not take me to the police station or nearest ATM, as he was threatening. Which leaves me wanting the share the following advice, when in Prague, use the metro. Now is when it really starts to get fun.

I arrive backstage. Backstage, unless you were with Guns and Roses in the mid 80's, is usually a place best avoided. The crew is either running around cursing under their breath because they've misplaced the hex wrench or can't fit everyone on the guest list or trying locate the one corner of the room that has decent enough wifi to skype their girlfriend and where the hell is their laptop anyway. You do not want to be in their way. Amanda first has to entertain 3 televised interviews in a row, including Czech MTV. As far as I can tell they all ask the exact same questions, but then again I'm helping myself to the cheese plate and miss most of it. Adrian Stout of the Tiger Lillies shows up, the self professed "World's most foremost Death Oompah band", who I remember as the only band at the Fringe Festival to feature a song about hamster buggery. They are, in short, a band worth getting to know.

As this Prague show is a last minute add-on, they do rock star sets instead of the more theatrical Evelyn and Evelyn, which is fine because it means more rowdy people can be packed in without the chairs lining the floor. Gaba Kulka who's down from Warsaw opens, then Jason plays. To me he's a bit like Tom Waits with a few of Ian Curtis's seizures thrown in. One of those, "I just smoked a pack of Camel straights with a quart of JD and I can't wait to do the same thing after lunch.." voices. But truly great songs.

Amanda is in fine form, covers Billie Jean, has Adrian on stage to play the musical saw (with a violin bow) to the Tiger Lillies "Flying Robert", and celebrates her tour manager's birthday with a sparkling cake followed by letting him sing "I Love How You Love Me" to send through youtube back to his boyfriend in Seattle who he still hasn't been able to skype. Then everyone gets on stage for the obligatory drinking song and the tour is over. Not quite, there's a sea of people who want merch (unfortunately the venue's poster sells out first) and various bits of things signed by the band who, despite being utterly knackered, are stand up enough to do it. Backstage Adrian and I use the puppets to celebrate with an impromptu "There Ain't Nobody Here but us Chickens" by Louis Jordan follwed by a hazy late night dinner that involved roast duck and some nice police officers, but I don't really remember.

The next day is drizzly so I take in the lovely Uměleckoprůmyslové Museum, which I think is Czech for "little old gorgeous things that look like a pain to polish". Lunch is at Ariana, a small Afghan restaurant that 13 of us literally crash like downloading every google map at once. It's not so much that there is only one waiter and even fewer people in the kitchen, it's more that said waiter is so starstruck by one of Jason's friends, a Czech celebrity, and more to the point that his hero has brought a pile of books for the boyfriend of the American girl with no eyebrows to sign. I thought the poor guy was going to wet himself, or at least take three hours to get the lunch out and forget my entree (he ended up 2 for 3, at least as far as I know).

Tuesday, March 16, 2010

Sometimes I really, really love my job. This is especially true when I get to leave it. It is ultimately true when I get to leave it for a place like Italy for a conference that they pay for. So here I am, in Venice, for 2 days before heading to the first annual European Zebrafish Primary Investigator Meeting in Padua.

I will gracefully omit the beginning part of the trip where I took the bus to the wrong train station and spent about an hour in some piazza turning in a slow circle staring at my Stupid iPhone. They say that getting lost in Venice is part of the whole experience, and boy, they do make it easy for you. About half of the streets dead end, the other half plunge you into the canal (the exposure risk of which, if I read correctly, is about equivalent of eating the brains of the Outbreak monkey).

I've been to Italy before, and can without hesitation say that this is pretty much exactly like the other trips magnified by an order of about ten thousand. There are hardly any Italian people here. Americans, check. You can spot an American in Europe without even seeing them, you just need to listen to any sentence that uses the word "like" 40 times. My favorite overheard Americans today were the couple of women looking into a store window, "Ooohh!! Helen! Wasn't that, like, the same one you bought at like, that other little store?" (it was a stressed-out grappa bottle), and the guy wearing the jester hat with bells loudly telling his friends about the last time he had a gun pulled on him. We are definitely a most unique breed. When living in Spain I often found myself speaking French so I wouldn't be confused with one of them, but I'm really not sure who I thought I was kidding.

So Venice is Tourist Town. Like no other. The insulation of the lagoon and surrounding waters has made it possible to strangle any indigenous anything out of the city and has left it a maze of boutiques selling carnival masks, glass baubles, and handbags. The masks are all made in China. Some of the glass baubles I saw, necklaces and paperweights and such, had "Murano Glass" printed on them, despite that fact that if they actually were real Murano glass the price would be about five hundred times the €10 tag. And the handbag stores, with their "Real Italian Leather" stamps were all run by, you guessed it, Chinese women.

This isn't a new development for me. In January I spent a week in Dahab, Egypt, and every little mosaic Persian-looking trinket in every shop was shipped from China. The only authentic souvenir I bought back from that trip was a rock I found on the beach. This fact was not half as disheartening as the traditional Bedouin desert party I went to with the Bedouin fire-grilled food, the Bedouin rebab music, and the guy dressed in the traditional Bedouin robes dancing with some chick wearing a red Nebraska Huskers sweatshirt.

And don't think for a moment that I don't know how outrageously selfish and silly it is for me to barge into a culture fresh from a Ryanair flight and expect it to be unaffected. Even Iraq and Azerbaijan have a McDonalds.

That said, I happen to be in a very lovely place. Lovely because it is old. And being one of above said Americans, I still jump up and down excitedly clapping my hands if presented with a building over 50 years old (maybe that's why we're all here). It's old, decrepit, and gorgeous. Seriously, I have never seen a city in more dire need of a re-pointing job than Venice.

But since I don't have to pony up the condo fee to pay for it, I can just admire it. Just like the rest of the like, tourists.

Tuesday, February 23, 2010

I was asked earlier yesterday what I would like to eat for dinner. I responded, as honestly and sweetly as I could, that I would like to eat the heads of my employees and drink their blood.

Make no mistake, I like the members of my lab (and the rest of the institute where I work) very much. There's something very steadfast and soothing about the Dutch that allows for things to happen like the complete collapse of their government over the weekend and nary more of a response than, "Ja, well, they didn't do much anyway..."

So perhaps I was in a bit of a haste when I elected to expand my group from 4 to 6 of us in the span of about 10 minutes. All this work! Who's going to do it? I want to go back to the safety of my office! Actually, that's not entirely true, my office is not completely mine, but a perfect example of the fact that the Netherlands has the highest population density in the world. I've had more space to myself playing Two Minutes in the Closet.

We're trying to get a paper out. Anyone in science (or perhaps any career where your net worth is strictly based on your publications) knows that for a job like this you set a deadline, and then add about 4 months. Ideally I would have had this out at Christmas. I believe Valentine's Day is long gone, March is tomorrow, and we still have two (ok, three) experiments to get done. This puts us back to about Thanksgiving, 2018.

My technician deciding to take a flying leap off of a 2 meter high wall and breaking both feet 3 weeks ago while on holiday didn't help. My feeble attempt to ban all holidays for the rest of the group got the well-deserved middle finger from my grad student who then went and plugged himself into a beer IV for a week. One of my masters students came up to me yesterday and said she felt nauseous and perhaps should go home, to which I almost responded, "Just stick your finger down your throat and get back to work..." But I didn't, so now she's down for the count. The darling new bachelor student in a flash of over-enthusiasm and perhaps also in sympathy for me having to do actual lab work, managed to maim a western blot, a northern gel, and an RNA isolation in one morning. Every PCR today failed, every sequencing submission. The climax of the day was knocking over my masters student's bucket of about 2 liters of melted ice onto her bench where she had left her lab notebook (to which I immediately thought, well, that will teach her to get nauseous and leave early). Who do I have to blame for this?

Myself, of course.

The horrible truth about molecular biology is that it hardly ever works. Any given experiment requires anywhere from 10 to hundreds of different buffers, antibodies, primers, etc, the malfunction of any which one results in another gel thrown in the disposal. Which might not be so bad if the actual process of getting to the disposal was a fun or enlightening one...it isn't. Most experiments require pipetting tiny volumes of liquid reagents into tiny tubes over, and over, and over. It's not far off from the factory worker who drills the same hole or seals the same box day in, day out. I take that back, at the end of the day, the factory worker can at least look at the successful stack of boxes or series of drilled holes...molecular biology doesn't even give up a reward at that level. Another tiny tube of clear liquid, or staring misty-eyed at another gel in the disposal, that's a typical ending of the molecular biologist's day.

The greatest mentor of my life, an MD in oncology, once described to me the difference between working in the lab and working in the hospital. He told me that walking into a hospital for work in the morning really sucks. It smells rank, everybody there is sick or injured or stressed. But at the end of the day you can leave with the sense that you've actually accomplished something, that you helped to improve the health and/or quality of life of some individuals, all of whom you could name. Going into the molecular biology lab in the morning on the other hand is usually pretty exciting. I'm going to start a cool experiment, I'm going to get results from that last experiment...and by the end of the day you're again looking at that damn disposal and considering leaving work via the ledge. Maybe some day your work will have an impact on the health of some individuals, maybe some gene function you help to clarify will eventually be considered when making a drug that enhances the longevity or quality of life for some people some years in the future. But you don't know this for sure and you certainly don't know their names. So all it really comes down to is where you publish and how much that determines your sense of self satisfaction. When moving to Europe I was confronted with the fact that I was going to hereon be judged by my "impact factor"...take the quality of the journals you've published in, which each have a numerical score determined by Dr. Godonlyknows, add them up and that's your worth. This wasn't the case in the US. Your publication list was important, of course, but it wasn't broken down so bluntly that you are just in fact, a number.

So back to why all these mistakes are my fault.

The precision required to get this job right is difficult to teach. Only after throwing your Nth gel out do you know why there were those streaks in the EtBr stain of the RNA...because you overloaded it. You have to allow your staff for mistakes, that is the only way they will learn.

Today went like this:

Every PCR worked, we cloned a gene ourselves that we then didn't have to order, and we got a lead in a screen that is exciting enough for me to want to start hyperventilating. I feel like I'm on top of the world, like I just scaled Everest, like I was Christian Laettner scoring the famous last 3 pointer against Kentucky in that semifinal NCAA round. I wanted to kiss every member of my staff and plaster them with gold stars. I no longer wish to drink their blood.

This is what we signed up for, the volatile stream of lows spliced infrequently with the highs of actually discovering something or figuring something out that no one in the history of humankind has ever done before. The feeling of which is indescribable.

Thursday, February 18, 2010

It's been so easy to put off the learning of Dutch for past 18 months. Who in the world would bother to learn a language that is only spoken in a square area the size of a postage stamp that also makes you hock luggies with every "g"? Add to the fact that everyone here speaks better English than I do, and my motivation to learn Dutch has been on par with dental work. It certainly doesn't help either that, knowing full well they speak better English than you, the Dutch will immediately switch if you brave it and try your rudimentary "Ik wil een witte wijn" and will respond with, "Would you like to try the Sonoma chardonnay?" This is most discouraging.

However when my colleague, another American and dear friend who has lived here for over 12 years with a very well established lab forwarded me the email solicitation for Dutch classes with following text in the body: "A-hem!", I finally felt obliged to go.

Class is once a week with a guy, Mickeal, who is a shaggy blond 27ish year old teaching this for the first time voluntarily for reasons I can't figure out except that maybe it's community service for a drunk driving incident. Tonight was the second class, held at his flat instead of the lovely academic building on the cobblestone street with canal running along the front. I had forgotten to do my homework, which I managed to weasel out of by emphatically agreeing that we study pronunciations for the class and do double homework corrections next week.

There's 8 of us in his living room, your typical partitioned shoebox with steep steps and no heat. We've got lists of words with common vowel combinations -ee, -ie, -oo, etc along with a mishmash of vocabulary examples. So now do I not only know that the Chinese restaurant down the street Leen is not pronounced "lean" but "lane" but I also know that "kukeleku" is what a rooster says.

I just can't wait to work that word into polite conversation.

The fact is that listening to Dutch is so close to American English I often mistake conversationalists to be from New Jersey when in fact they're from Rotterdam. The accent is practically the same, and so many of the words sound the same. Although they do spell them in a very silly way...we played Scrabble in a pub once and the most common letters after E were J's and Z's. Still, it's been getting easier to understand people, and I can definitely feel for the tantrum-ridden two year old who can get what's being said and still not be able to speak a word.

Some of the other vocab words on the work sheet which I'm sure to use daily include "luik" (shutter), "zeis" (sickle) and two words "luk" and "lak" which apparently were so arcane the teacher didn't even know them.

This is not to say that no relevant words were taught, I now know how to say I ride on my bike ("Ik rijd op mijn fiet") and that the weather sucks ("het weer is rot").

We'll see how the rest of the course goes. Rumor has it that there's a convent in the country where they lock you up for two weeks and you emerge speaking fluently. Despite the fact that this course method may well consist of kneeling on bricks and self flogging, it would be worth it to be able to say back to the bartender, "Nee, geef mij een biertje, ik haat chardonnay".

Monday, February 15, 2010

Today my second masters student started. My technician is home with two broken feet and my grad student is drunk in a ditch somewhere wearing a Kermit the Frog costume (it's carnival time in his hometown of Masstricht). Meaning that despite having a prolific group consisting of 6 of us now, I was forced out of my comfy office where for the last year I've been happily staring at Pubmed abstracts and back into the lab to do actual work. So I ran a northern gel. Overloaded it and had to pitch it. Another 2.4g of agarose down the drain.

There really should be some cut off point for group leaders after which they are no longer allowed back in the lab to do real work.

The background goes like this: My postdoc was at MIT, about 20 minutes away from where I grew up. Having boomeranged back to the Boston area more times than I care to count, coupled with a nasty divorce and the fact that no one in the states was hiring group leaders 2 years ago, I got out. As far as I could. The next thing I knew I was living in a country where they fry gravy and serve it with mayo (this would be the Netherlands).

I'm here. I love it. I hate it. I love it more.

The group leader position is by far and away the most difficult job I've every had. As a grad student and postdoc you are driven solely by yourself. No one particularly cares when you graduate, as evidenced by the shocking number of students at Duke (where I did my PhD) who have been mired there for 9 years. (I will always admire the one guy who quit because he won a game show). Now the powers that be want a return on their investment. I have no idea how much cash was spent on me to set the lab up, but my guess is that it is upwards of an amount that could bail out Greece.

So what is the purpose of this, aside from being tired of sharing my witty remarks about culture shock through individual emails. One is that I love to write. Two is that I would like those starting positions like mine to know that it's probably like this for everyone, the sense of intense excitement followed by acute panic (I mentioned this to a colleague of mine who replied that he was still waiting for the intense excitement to kick in). Three is that it's hard to be in close touch with everyone back in the states. So...